Abstract

Background

Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing
processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal
and plastic composite materials. They are classified as high aspect ratio nanomaterials.
Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols.

Methods

Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm.
The aluminum content found in this nanomaterial was 30% [mixed phase material containing
Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day,
5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were
aerosolized with an acoustical dry aerosol generator that included a grounded metal
elutriator and a venturi aspirator to enhance deagglomeration. Average concentration
of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure)
were necropsied immediately after the last exposure. Aluminum content in the lung,
heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed
by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential
cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood
(total and differential cell counts), lung histopathology and pulmonary mechanics.

Results

Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry
wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells
and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times
higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found
and neutrophils were below 1% in all groups. No significant differences were found
in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α,
and MIP-2) between shams and exposed mice.

Conclusions

Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased
lung macrophages, but no inflammatory or toxic responses were observed.